| Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1. | |
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MedLine Citation:
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PMID: 20527046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes beta cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. METHODS: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. RESULTS: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean + or - SEM) in untreated rats occurred at 56.5 + or - 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 + or - 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting beta cells. CONCLUSIONS: Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs. |
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Authors:
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Ofer Yanay; Daniel Moralejo; Kelly Kernan; Margaret Brzezinski; Jessica M Fuller; Randall W Barton; Ake Lernmark; William R Osborne |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of gene medicine Volume: 12 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-10-08 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
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Languages: eng Pagination: 538-44 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Washington, Seattle, WA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / drug effects* Cell Proliferation / drug effects Diabetes Mellitus, Experimental / diagnosis, metabolism*, physiopathology, therapy* Female Glucagon / metabolism Glucagon-Like Peptide 1* / pharmacology, therapeutic use Humans Implants, Experimental Male Muscle, Smooth, Vascular / cytology Myocytes, Smooth Muscle / cytology, physiology Pancreas / cytology, metabolism Rats Rats, Inbred BB* Rats, Wistar Transduction, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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AI42380/AI/NIAID NIH HHS; DK17047/DK/NIDDK NIH HHS; R01 DK067221-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 89750-14-1/Glucagon-Like Peptide 1; 9007-92-5/Glucagon |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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